Low dose of weight loss drug may improve heart failure symptoms with minimal weight loss

• Low doses of the injectable weight-loss medication semaglutide helped improve symptoms of heart failure with preserved ejection fraction (HFpEF) when tested in two types of animals able to closely mimic heart failure in humans. Improvements were seen directly in the heart and blood vessels, even among the animals that had no significant weight loss.

• If future research confirms these results in humans, low-dose semaglutide may be a treatment option for people with heart failure who do not need to lose weight or who cannot tolerate the standard doses of semaglutide. It could also be suitable for people with other heart-related diseases who do not have obesity.

• Note: The study featured in this news release is a research abstract. Abstracts presented at the American Heart Association’s scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.

• Embargoed until 7 a.m. CT/8 a.m. ET, Wednesday, July 23, 2025

  BALTIMORE, July 23, 2025 — Low doses of the injectable weight-loss medication semaglutide may improve symptoms of a hard-to-treat type of heart failure. This effect happened through direct action on the heart muscle and blood vessels, despite resulting in no significant weight loss, according to preliminary research presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2025. The meeting, held in Baltimore, July 23–26, 2025, offers the latest research on innovations and discovery in cardiovascular science.

  Heart failure occurs when the heart is unable to pump enough oxygen-rich blood to meet the body’s needs, resulting in shortness of breath, fatigue and other symptoms. One type of left-sided heart failure, called diastolic failure, occurs when the left ventricle can’t relax normally because the muscle has stiffened. As a result, the heart can’t fill with blood as it should during the time in between each heartbeat. This is known as heart failure with preserved ejection, or HFpEF.

  “HFpEF is a major and growing health concern, accounting for about half of all heart failure cases. It’s becoming more common as our population ages and as more people are diagnosed with conditions like high blood pressure, Type 2 diabetes and obesity,” said study author Mahmoud Elbatreek, Ph.D., a postdoctoral scientist in the department of cardiac surgery at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles.

  Many people with HFpEF also have obesity. Currently, the U.S. Food and Drug Administration (government agency that regulates food, drugs, tobacco and other public health issues) has not approved semaglutide for the treatment of HFpEF. In a clinical trial published in 2023, the STEP-HFpEF trial, weekly injections of a standard dose of semaglutide significantly reduced symptoms in people with obesity and HFpEF, boosted their exercise capacity and improved their quality of life. “However, one big question remained: Is semaglutide’s main benefit simply due to weight loss, or does it also have a direct, positive effect on the heart and blood vessels?” Elbatreek said.

  In the new study, Elbatreek and colleagues used two animal models that closely mimic humans with HFpEF. Rats genetically prone to obesity, and pigs were treated to induce high blood pressure and fed a salty, fatty diet. To observe the direct effect of semaglutide on the heart and blood vessels independent of its well-known weight loss effect, the animals were separated into two groups: one group received weekly injections of a low dose of semaglutide and the second group, the control group, received a placebo injection.

  The study found that, despite resulting in no significant weight loss, the low-dose semaglutide treatment resulted in:

  • higher exercise capacity (by 58%);

  • improvement in the ventricle’s ability to relax and fill with blood (by 61%);

  • less scarring in the heart (by 37%);

  • reduced fat within the heart and liver (by 65% and 42%, respectively); and

  • better blood vessel function (by 52%). (For assessment details, please see study background Information below.)